Mucosal MelanomaPhase 2NCT04622566
Lenvatinib and Pembrolizumab in Resectable Mucosal Melanoma
A Phase 2 study testing Lenvatinib, Pembrolizumab in people with Mucosal Melanoma and Neoadjuvant Treatment, run by Peking University Cancer Hospital & Institute at 1 site in China.
Trial summary
This study is a randomized ,single center clinical study which is designed to investigate whether combination of Pembrolizumab with Lenvatinib could improve pCR rate and consequent survival in resectable mucosal melanoma. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Mucosal Melanoma, Neoadjuvant Treatment
- What is being tested?
- Lenvatinib, Pembrolizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteChina
- Study dates
- 30 Dec 2020to 30 Dec 2023
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Be willing and able to provide written informed consent for the trial. 2. Be a male or female subject and is 18-75 years of age on day of signing informed consent.
- 3. Have histologically or cytologically confirmed resectable mucosal melanoma. Only cases where a complete surgical resection with tumour-free margins can safely be achieved, as assessed by the surgeon, are defined as resectable.
- 4. Newly diagnosed melanoma without any previous anti-cancer treatment 5. Patients must be able to provide a biopsy at baseline 6. Able to swallow and retain oral medication 7. Be medically fit enough to undergo surgery as determined by the treating medical and surgical oncology team 8. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 10 days of treatment initiation.
- 9. Demonstrate adequate organ function as defined in Table 1. All screening labs should be performed within 1 week prior to treatment initiation.
- 10. Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mmHg at screening and no change in antihypertensive medications within 1 week before treatment initiation.
- 11. Males and female subjects of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 120 days after the last dose of study medication.
- 12. (Female subject of childbearing potential) Have a negative urine or serum pregnancy test within 1 week prior to receiving the first dose of study medication. If the urine test is positive or borderline a serum pregnancy test will be required.
Who cannot join
- 1. Has a known additional malignancy that is progressing or requires active treatment, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
- 2. Has known central nervous system (CNS) metastases and/or carcinomatous meningitis.
- 3. Has received any prior systemic anti-cancer treatment for melanoma 4. Has received prior lenvatinib 5. Has received prior therapy with an anti-PD-1 or anti-PD-L1 agent 6. Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 4 weeks of the first dose of treatment in this current trial.
- Note: subject should be excluded if he/she received an investigational agent with anti-cancer or anti-proliferative intent within the last 12 months.
- 7. Has received a live vaccine within 30 days of the first dose of study treatment.
- Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., FluMist ®) are live attenuated vaccines, and are not allowed.
Show all 24Show fewer
- 8. Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
- 9. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 1 week prior to the first dose of trial treatment.
- 10. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- 11. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- 12. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis 13. Has an active infection requiring systemic therapy. 14. Has presence of gastrointestinal condition including malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib.
- 15. Has had a major surgery within 4 weeks prior to initiation of treatment. Adequate wound healing after major surgery must be assessed clinically and have resolved completely.
- 16. Has a pre-existing Grade ≥3 gastrointestinal or non-gastrointestinal fistula.
- 17. Has radiographic evidence of major blood vessel invasion/infiltration. The degree of tumor invasion/infiltration of major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy.
- 18. Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug.
- 19. Has clinically significant cardiovascular disease within 12 months of the first dose of study intervention including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.
- Note: Medically controlled arrhythmia would be permitted. 20. Has urine protein ≥1 g/24-hour. Note: Participants with >1+ proteinuria on urine dipstick will undergo 24-hour urine collection for quantitative assessment of proteinuria.
- 21. Has prolongation of QTc interval (calculated using Fridericia's formula) to >480 msec.
- 22. Has left ventricular ejection fraction (LVEF) below the institutional normal range as determined by multi-gated acquisition scan (MUGA) or echocardiogram.
- 23. Has a history or current evidence of any condition, therapy, lab abnormality or other circumstance that might expose the subject to risk by participating in the trial, confound the results of the trial, or interfere with the subject's participation for the full duration of the trial.
- 24. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- 25. Is pregnant or breastfeeding or expecting to conceive children within the projected duration of the trial, starting with the screening visit through 6 months after the last dose of study medication.
- 26. Has a known hypersensitivity to the components of the study therapy or its analogs.
- 27. Has a known history of active TB (Bacillus Tuberculosis) Female participants who are breastfeeding are not eligible for enrollment
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Phase II Study of Neoadjuvant Lenvatinib and Pembrolizumab in Resectable Mucosal Melanoma
This study is a randomized ,single center clinical study which is designed to investigate whether combination of Pembrolizumab with Lenvatinib could improve pCR rate and consequent survival in resectable mucosal melanoma.
All the eligible patients were assigned to receive Lenvatinib once a day (QD) for 6 weeks plus pembrolizumab on Day 1 of each 21-day cycle (Q3W) concurrently on days 1 and 22, followed by surgery and 18 cycles of Pembrolizumab 200mg q3w of adjuvant phase.
Read the detailed description
Mucosal melanoma is a rare type of melanoma in Caucasian population and a dominate subtype in Asia, which generally carries a worse prognosis than cutaneous melanoma. Surgery remains the primary therapeutic intervention for mucosal melanoma, and neoadjuvant therapy is still needed which can lead to improvements in outcomes by surgical resectability, local control and organ preservation.
Immunotherapy has showed promising activity in advanced melanoma. However, PD-1 antibodies, both Pembrolizumab and Nivolumab, showed much poorer response to mucosal melanoma than to cutaneous melanoma.
Pembrolizumab showed modest objective response rate (ORR, 13%) in advanced mucosal melanoma in Chinese population (NCT02628067). Recent study also demonstrated that neoadjuvant therapy with one dose of Pembrolizumab could lead to pathological complete response (pCR) or major response in nearly 30% of resectable advanced melanoma and pCR was associated with reduced risk of recurrence and improved survival.
Lenvatinib is also a kinase inhibitor that inhibits the kinase activities of VEGFR1,2, 3 which has been approved by FDA for differentiated thyroid cancer, advanced renal cell carcinoma and hepatocellular carcinoma.
It is hypothesized that neoadjuvant Pembrolizumab in combination with Lenvatinib could result in higher anti-tumor activity with lower toxicity and prolong RFS and OS in high-risk resectable mucosal melanoma.
The study will assess the efficacy and safety of the combination Pembrolizumab and Lenvatinib as neoadjuvant treatment in resectable mucosal melanoma.
- Conditions
- Mucosal Melanoma, Neoadjuvant Treatment
- Being tested
- Lenvatinib, Pembrolizumab
- Keywords
- pembrolizumab, Lenvatinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lenvatinib, PembrolizumabDrug
Also called Biological: Pembrolizumab IV infusion Other Names: MK-3475; KEYTRUDA®, Drug: Lenvatinib Oral capsule Other Names: MK-7902; E7080; LENVIMA®
After enrollment, patients receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for 6 weeks; Lenvatinib 20mg orally once daily for 6 weeks. Patients conduct surgery within 1-4 weeks after the last dose of Pembrolizumab and Lenvatinib. After complete surgery, Pembrolizumab will be as adjuvant treatment for up to 15 cycles, 200mg IV on day 1 of every 21 day-cycles.
| Study group | Role | What they receive |
|---|---|---|
| Lenvatinib and Pembrolizumab in Resectable mucosal Melanoma. | Experimental | Not described Receives: Drug: Lenvatinib, Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological complete response (pCR) rate: defined as the percentage of subjects without alive tumor cells in the resected specimen post operation.
To evaluate pathological complete response (pCR) rate of Pembrolizumab combined with Lenvatinib as neoadjuvant therapy for resectable mucosal melanoma.
Measured: Approximately 10 weeks
Secondary outcomes (3)
1 year RFS (recurrence-free survival) rate per RECIST1.1 as Assessed by investigator
To evaluate1-year RFS rate of Pembrolizumab combined with Lenvatinib as neoadjuvant therapy for resectable mucosal melanoma.
Measured: Approximately 1 year
Overall survival
OS is defined as the time from date of randomization to date of death from any cause. OS will be presented.
Measured: Approximately 2 years
Incidence of AEs/SAEs
Adverse events (AEs) ; serious adverse events (SAEs); abnormal value of Lab test according to NCI-CTCAE V5.0
Measured: Approximately 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2020
- Study start30 Dec 2020 (estimated)
- Primary completion30 Dec 2021 (estimated)
- Study completion30 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mucosal MelanomaStudies of the same condition, open and under way.
- More trials run by Peking University Cancer Hospital & InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University Cancer Hospital & Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jun Guo, Peking University Cancer Hospital & Institute
- Investigators
- Jun Guo, MD, Principal investigator, Peking University Cancer Hospital & Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04622566
- Sponsor's protocol ID
- MK59132
- Status last verified
- Nov 2020
- First submitted
- 28 Oct 2020
- Last updated
- 13 Nov 2020
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Neoadjuvant Lenvatinib and Pembrolizumab in Resectable Mucosal Melanoma
- ClinicalTrials.gov ID
- NCT04622566
- Acronym / sponsor ID
- MK59132
- Conditions
- Mucosal Melanoma, Neoadjuvant Treatment
- Keywords
- pembrolizumab, Lenvatinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 26 participants (estimated)
- Lead sponsor
- Peking University Cancer Hospital & InstituteUniversity, hospital or other
- Study start
- 30 Dec 2020 (estimated)
- Primary completion
- 30 Dec 2021 (estimated)
- Study completion
- 30 Dec 2023 (estimated)
- First posted
- 10 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a randomized ,single center clinical study which is designed to investigate whether combination of Pembrolizumab with Lenvatinib could improve pCR rate and consequent survival in resectable mucosal melanoma.
All the eligible patients were assigned to receive Lenvatinib once a day (QD) for 6 weeks plus pembrolizumab on Day 1 of each 21-day cycle (Q3W) concurrently on days 1 and 22, followed by surgery and 18 cycles of Pembrolizumab 200mg q3w of adjuvant phase.
Detailed description
Mucosal melanoma is a rare type of melanoma in Caucasian population and a dominate subtype in Asia, which generally carries a worse prognosis than cutaneous melanoma. Surgery remains the primary therapeutic intervention for mucosal melanoma, and neoadjuvant therapy is still needed which can lead to improvements in outcomes by surgical resectability, local control and organ preservation.
Immunotherapy has showed promising activity in advanced melanoma. However, PD-1 antibodies, both Pembrolizumab and Nivolumab, showed much poorer response to mucosal melanoma than to cutaneous melanoma.
Pembrolizumab showed modest objective response rate (ORR, 13%) in advanced mucosal melanoma in Chinese population (NCT02628067). Recent study also demonstrated that neoadjuvant therapy with one dose of Pembrolizumab could lead to pathological complete response (pCR) or major response in nearly 30% of resectable advanced melanoma and pCR was associated with reduced risk of recurrence and improved survival.
Lenvatinib is also a kinase inhibitor that inhibits the kinase activities of VEGFR1,2, 3 which has been approved by FDA for differentiated thyroid cancer, advanced renal cell carcinoma and hepatocellular carcinoma.
It is hypothesized that neoadjuvant Pembrolizumab in combination with Lenvatinib could result in higher anti-tumor activity with lower toxicity and prolong RFS and OS in high-risk resectable mucosal melanoma.
The study will assess the efficacy and safety of the combination Pembrolizumab and Lenvatinib as neoadjuvant treatment in resectable mucosal melanoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lenvatinib and Pembrolizumab in Resectable mucosal Melanoma. | Experimental | Drug: Lenvatinib, Pembrolizumab |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 1. Be willing and able to provide written informed consent for the trial. 2. Be a male or female subject and is 18-75 years of age on day of signing informed consent.
- 3. Have histologically or cytologically confirmed resectable mucosal melanoma. Only cases where a complete surgical resection with tumour-free margins can safely be achieved, as assessed by the surgeon, are defined as resectable.
- 4. Newly diagnosed melanoma without any previous anti-cancer treatment 5. Patients must be able to provide a biopsy at baseline 6. Able to swallow and retain oral medication 7. Be medically fit enough to undergo surgery as determined by the treating medical and surgical oncology team 8. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 10 days of treatment initiation.
- 9. Demonstrate adequate organ function as defined in Table 1. All screening labs should be performed within 1 week prior to treatment initiation.
- 10. Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mmHg at screening and no change in antihypertensive medications within 1 week before treatment initiation.
Key exclusion criteria (24 listed)
- 1. Has a known additional malignancy that is progressing or requires active treatment, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
- 2. Has known central nervous system (CNS) metastases and/or carcinomatous meningitis.
- 3. Has received any prior systemic anti-cancer treatment for melanoma 4. Has received prior lenvatinib 5. Has received prior therapy with an anti-PD-1 or anti-PD-L1 agent 6. Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 4 weeks of the first dose of treatment in this current trial.
- Note: subject should be excluded if he/she received an investigational agent with anti-cancer or anti-proliferative intent within the last 12 months.
- 7. Has received a live vaccine within 30 days of the first dose of study treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lenvatinib, PembrolizumabAlso: Biological: Pembrolizumab IV infusion Other Names: MK-3475; KEYTRUDA®, Drug: Lenvatinib Oral capsule Other Names: MK-7902; E7080; LENVIMA®After enrollment, patients receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for 6 weeks; Lenvatinib 20mg orally once daily for 6 weeks. Patients conduct surgery within 1-4 weeks after the last dose of Pembrolizumab and Lenvatinib. After complete surgery, Pembrolizumab will be as adjuvant treatment for up to 15 cycles, 200mg IV on day 1 of every 21 day-cycles. | Drug | Lenvatinib and Pembrolizumab in Resectable mucosal Melanoma. |
Primary outcome
Pathological complete response (pCR) rate: defined as the percentage of subjects without alive tumor cells in the resected specimen post operation.
Time frame: Approximately 10 weeks
To evaluate pathological complete response (pCR) rate of Pembrolizumab combined with Lenvatinib as neoadjuvant therapy for resectable mucosal melanoma.
3 secondary outcomes
1 year RFS (recurrence-free survival) rate per RECIST1.1 as Assessed by investigator
Time frame: Approximately 1 year
Overall survival
Time frame: Approximately 2 years
Incidence of AEs/SAEs
Time frame: Approximately 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jun Guo, MD principal investigator
Peking University Cancer Hospital & Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lenvatinib, Pembrolizumab in people with Mucosal Melanoma and Neoadjuvant Treatment, run by Peking University Cancer Hospital & Institute at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 13 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jun Guo, MD (86-10-88196317, guoj307@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathological complete response (pCR) rate: defined as the percentage of subjects without alive tumor cells in the resected specimen post operation. (time frame: Approximately 10 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2020.